中文摘要
基于连翘有效部位及其结构新颖单体化合物在神经保护方面体现出的优良活性,本项目拟采用不同的特异性药物靶标跟踪筛选并结合现代微量、快速、在线等集成的分离分析方法,构建以活性结果和紫外光谱特征为指导的靶向分离策略,对常用中药连翘活性分子群进行系统研究,在此基础上,利用已建立的体内外活性筛选平台,重点考察这些化合物对鱼藤酮、脂多糖、β淀粉样肽损伤PC12细胞的保护作用,并探讨其对1)氧化应激、2)神经炎症、3)由于氧化应激及神经炎症所导致的线粒体功能损伤的影响,进行构效关系研究。结合体内活性评价,诠释连翘在神经保护方面的药效物质基础,同时获得具有神经保护活性作用的活性物质基本结构特征,结合构效关系研究优选出同时具有新颖结构和高活性的先导化合物,为创新药物研究提供先导结构,为进一步开发具有自主知识产权的新型药物奠定基础。
英文摘要
Based on the neuroprotection activity of the active fraction and novel chemicalconstituents from Forsythia suspensa in vivo and in vitro, this project plans to systematically study its active constituents by using target tracing isolation combining with pharmacological results and the fast, microamount, online isolation and analysis methods. At the same time, the project will investigate the neuroprotection activity of these compounds against rotenone, lipopolysaccharide, or β-amyloid induced toxicity in PC12, and the influence on 1) oxidative stress, 2) neuro-inflammatory, and 3) mitochondrial damage. On the basis of these findings, their structure-activities relationship will be summarized. With the evaluation of animal models assay in vivo, the bioactive substances with neuroprotective from Forsythia suspensa would be clarified and the basic chemical structure features of compounds might be obtained. Eventually, the bioactive compound would be a lead in drug discovery and a base of a new drug with independent intellectual property.
